Causation When do we have enough evidence? Sam Bracebridge.
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Transcript of Causation When do we have enough evidence? Sam Bracebridge.
CausationWhen do we have enough evidence?
Sam Bracebridge
It is not the fall that kills you. It is
the sudden stop at the end.
Douglas Adams
Learning outcomes
By the end of the lecture you will be able to:
•List the Bradford-Hill criteria for causal
inference
•Advise if radioactivity from the Sellafield
nuclear plant causes childhood leukaemia
Sellafield nuclear plant
Anecdotal evidence
• Journalist: documentary on occupational
exposure
• Local population: higher number of cases
of childhood leukaemia (CL)
• Broadcast: excess CL due to radioactive
environmental contamination
LOCAL ANGER!!!!
National Media
Government Action
Enquiry:
“Do radioactive discharges from
Sellafield cause childhood
leukaemia?”
Causal inference
Bradford Hill’s criteria (1965)
Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
Temporal Relationship
Exposure must precede disease
Essential criterion for causality
Knowledge of:
• Latency period
• Incubation period
Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
Strength of Association
Strong associations are more likely to be causal than weak ones
Smoking > 20 cigarettes/day
laryngeal carcinoma (RR 20)
BUT
• Bias, confounding?
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Biologic Plausibility
Is consistent with current biological and medical common knowledge.
Smoking
Ingesting of chemicals and known carcinogens
DNA mutations
lung cancer
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Dose-response Relationship
Risk increases with more intense/more frequent exposure
But:
• Beware threshold doses
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Effect of removing the exposure
A decrease in the outcome of interest is seen when the exposure is removed
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
Specificity of the association
Strengthens evidence if the cause has ONLY one effect.
Asbestos exposure mesothelioma
abestosis
lung cancer
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Alternate explanations considered
8. Specificity of the association
9. Consistency with other knowledge
L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008
YOU ARE ASKED TO GIVE AN EXPERT OPINION
Does radioactivity from Sellafield cause childhood leukaemia?
Exercise
• Read the paper
• Which criteria are reached?
• What is your conclusion ?
• What is your recommendation?
Gardner M. Father’s occupational exposure to radiation and the raised level of childhood leukaemia near the Sellafield nuclear plant. Env Health Perspectives. Vol 94, 5-7, 1991.
Rothman KJ; Epidemiology: an introduction. Oxford University Press 2002, 94-101
References